title: The clinical course of treated hyperparathyroidism among patients receiving hemodialysis and the effect of cinacalcet: the EVOLVE trial.
abstract: BACKGROUND
  The clinical course of secondary hyperparathyroidism (sHPT) in patients on hemodialysis is not well described, and the effect of the calcimimetic cinacalcet on disease progression is uncertain.
  
  
  OBJECTIVE
  Our objective was to describe 1) the clinical course of sHPT in patients treated with phosphate binders and/or vitamin D sterols and 2) the impact of cinacalcet on the occurrence of severe unremitting HPT, defined by the persistence of markedly elevated PTH concentrations together with hypercalcemia or parathyroidectomy (PTX).
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, global, multicenter clinical trial.
  
  
  METHODS
  Of 5755 patients screened with moderate to severe sHPT, 3883 patients on hemodialysis were included in the trial.
  
  
  METHODS
  Outcomes included PTX; severe, unremitting HPT; and use of commercial cinacalcet (a protocol violation).
  
  
  METHODS
  Intervention was cinacalcet (30-180 mg daily) or placebo for up to 64 months.
  
  
  RESULTS
  In the 1935 patients randomized to placebo, 278 patients (14%) underwent PTX (median PTH 1872 pg/mL within the previous 12 weeks from surgery). Age, sex, geographic region, co-morbidity, calcium-containing phosphate binder use, and baseline serum calcium, phosphorus, and PTH concentrations were associated with PTX. Commercial cinacalcet was started in 443 (23%) patients (median PTH 1108 pg/mL before treatment began). Severe unremitting HPT developed in 470 patients (24%). In a multivariable Cox model, the relative hazard (comparing patients randomized to cinacalcet versus placebo) of severe unremitting HPT was 0.31 (95% confidence interval = 0.26-0.37). The relative hazard differed little when adjusted by baseline clinical characteristics.
  
  
  CONCLUSIONS
  Severe unremitting HPT develops frequently in patients on hemodialysis despite conventional therapy, and cinacalcet substantially reduces its occurrence.
authors.affiliation: MD, Health Sciences Center, Memorial University, St John's, Newfoundland, Canada A1B 3V6. pparfrey@mun.ca.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.forename: Ricardo
authors.initials: R
authors.lastname: Correa-Rotter
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Charles A
authors.initials: CA
authors.lastname: Herzog
authors.forename: Gerard M
authors.initials: GM
authors.lastname: London
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.forename: Bastian
authors.initials: B
authors.lastname: Dehmel
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Trotman
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Modafferi
authors.forename: William G
authors.initials: WG
authors.lastname: Goodman
mesh_terms: D000328:Adult; D000368:Aged; D001851:Bone Diseases, Metabolic / Q000503:physiopathology / Q000628:therapy*; D057966:Calcimimetic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069449:Cinacalcet; D003131:Combined Modality Therapy / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000517:prevention & control; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage / Q000627:therapeutic use*; D016105:Parathyroidectomy / Q000009:adverse effects; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects*; D012720:Severity of Illness Index
chemical_list: D057966:Calcimimetic Agents; D009281:Naphthalenes; D000069449:Cinacalcet